The Immunometabolic Bridge: Targeting Metainflammation to Prevent the Transition from Obesity to Cardiovascular...

Obesity and cardiovascular disease are linked by more than excess adiposity. They are connected through a chronic, low-grade inflammatory state that determines who progresses from risk to overt disease. We propose that metainflammation, arising from adipose tissue dysfunction and metabolic surplus, constitutes a key immunometabolic bridge between preclinical obesity and clinical cardiovascular disease. A central tenet of this framework is that metainflammation acts as a contributory driver of this transition; however, its pathogenic potential is realized only within a permissive metabolic environment marked by dyslipidaemia, insulin resistance, and genetic susceptibility. The intensity and persistence of this inflammatory state are governed by three interdependent mechanisms: immune cell heterogeneity within adipose tissue, mitochondrial dysfunction with associated redox stress, and cellular senescence driving a pro-inflammatory secretory phenotype-all sustained by impaired resolution pathways. Epidemiological and genetic evidence supports this dual requirement, demonstrating that inflammation requires a conducive metabolic milieu to precipitate clinical events. This conceptual framework translates directly into a tiered clinical strategy: identifying individuals with a high-inflammatory preclinical obesity phenotype, followed by a stepped intervention approach-from lifestyle modification and statins, highlighting their pleiotropic anti-inflammatory effects, to dual-benefit GLP‑1 receptor agonists, and ultimately to senolytic therapies that target the senescent cell root cause. Screening biomarkers such as hsCRP and IL‑6 can help identify high‑risk individuals. By redefining the trajectory from preclinical to clinical obesity as an immunometabolic continuum and providing actionable strategies to dismantle this bridge before end-organ damage, this framework offers a paradigm shift in the primary prevention of obesity-related cardiovascular disease.